Candida parapsilosis and the neonate: epidemiology, virulence and host defense in a unique patient setting

Invasive candidiasis is a common problem in premature infants that leads to high morbidity and mortality. Although Candida albicans has historically been the most prominent species involved in these infections and has therefore been the subject of the most study, Candida parapsilosis is increasing in frequency, and neonates are disproportionately affected. This article reviews unique aspects of the epidemiology of this organism as well as strategies for prophylaxis against invasive candidiasis in general. Additionally, important differences between C.parapsilosis and C.albicans are coming to light related to virulence determinants and interactions with components of host immunity. These developments are reviewed while highlighting the significant gaps in our understanding that remain to be elucidated.

[1]  D. Kaufman,et al.  Changing Incidence of Candida Bloodstream Infections Among NICU Patients in the United States: 1995–2004 , 2006, Pediatrics.

[2]  David W Williams,et al.  Adherence and biofilm formation of non-Candida albicans Candida species. , 2011, Trends in microbiology.

[3]  R. Faix Invasive neonatal candidiasis: comparison of albicans and parapsilosis infection. , 1992, The Pediatric infectious disease journal.

[4]  D. Kaufman,et al.  Fluconazole prophylaxis against fungal colonization and infection in preterm infants. , 2001, The New England journal of medicine.

[5]  P. Smith,et al.  The use of antifungal therapy in neonatal intensive care. , 2012, Clinics in perinatology.

[6]  G. Quindós,et al.  In vitro activities of natural products against oral Candida isolates from denture wearers , 2011, BMC complementary and alternative medicine.

[7]  G. Butler,et al.  Phenotype switching affects biofilm formation by Candida parapsilosis. , 2005, Microbiology.

[8]  J. Sobel,et al.  Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[9]  M. Pfaller,et al.  Use of Epidemiological Cutoff Values To Examine 9-Year Trends in Susceptibility of Candida Species to Anidulafungin, Caspofungin, and Micafungin , 2010, Journal of Clinical Microbiology.

[10]  S. Filler,et al.  Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells , 2007, PLoS biology.

[11]  L. Saiman,et al.  Risk factors for candidemia in Neonatal Intensive Care Unit patients , 2000, The Pediatric infectious disease journal.

[12]  L. Saiman,et al.  Epidemiology of Candidemia at a Children's Hospital, 2002 to 2006 , 2009, The Pediatric infectious disease journal.

[13]  P. Mann,et al.  Impact of Antifungal Prophylaxis on Colonization and Azole Susceptibility of Candida Species , 2009, Antimicrobial Agents and Chemotherapy.

[14]  E. Beltrão,et al.  Adherence of Candida albicans and Candida parapsilosis to epithelial cells correlates with fungal cell surface carbohydrates , 2011, Mycoses.

[15]  David W Williams,et al.  Biofilms of non-Candida albicans Candida species: quantification, structure and matrix composition. , 2009, Medical mycology.

[16]  K. Yuen,et al.  Antifungal Susceptibility and Virulence Attributes of Bloodstream Isolates of Candida from Hong Kong and Finland , 2011, Mycopathologia.

[17]  S. Simmens,et al.  Incidence of Candida parapsilosis colonization in an intensive care nursery population and its association with invasive fungal disease , 1994, The Pediatric infectious disease journal.

[18]  A. Gácser,et al.  The Stearoyl-Coenzyme A Desaturase 1 Is Essential for Virulence and Membrane Stress in Candida parapsilosis through Unsaturated Fatty Acid Production , 2010, Infection and Immunity.

[19]  M. Rouabhia,et al.  Normal Human Gingival Epithelial Cells Sense C. parapsilosis by Toll-Like Receptors and Module Its Pathogenesis through Antimicrobial Peptides and Proinflammatory Cytokines , 2010, Mediators of inflammation.

[20]  D. Wildemeersch,et al.  Number of sites of perinatal Candida colonization and neutropenia are associated with nosocomial candidemia in the neonatal intensive care unit patient , 2010, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[21]  R. Ryan,et al.  Vertical and Horizontal Transmission of Candida albicans in Very Low Birth Weight Infants Using DNA Fingerprinting Techniques , 2008, The Pediatric infectious disease journal.

[22]  S. Challacombe,et al.  A Biphasic Innate Immune MAPK Response Discriminates between the Yeast and Hyphal Forms of Candida albicans in Epithelial Cells , 2010, Cell host & microbe.

[23]  G. González,et al.  Trends in Species Distribution and Susceptibility of Bloodstream Isolates of Candida Collected in Monterrey, Mexico, to Seven Antifungal Agents: Results of a 3-Year (2004 to 2007) Surveillance Study , 2008, Journal of Clinical Microbiology.

[24]  P. Taylor,et al.  Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infection , 2009, The Journal of experimental medicine.

[25]  N. Prasadarao,et al.  Mechanisms of Candida albicans Trafficking to the Brain , 2011, PLoS pathogens.

[26]  Deepak Kumar,et al.  Dexamethasone Therapy and Candida Sepsis in Neonates Less Than 1250 Grams , 2002, Journal of Perinatology.

[27]  D. Stevens,et al.  Candida parapsilosis fungemia in neonates: genotyping results suggest healthcare workers hands as source, and review of published studies , 2007, Mycopathologia.

[28]  N. Cerikcioglu,et al.  Acid proteinase, phospholipase, and biofilm production of Candida species isolated from blood cultures , 2007, Mycopathologia.

[29]  M. Yalaz,et al.  Successful caspofungin treatment of multidrug resistant Candida parapsilosis septicaemia in an extremely low birth weight neonate , 2006, Mycoses.

[30]  T. Kuijpers,et al.  Complement Receptor 3 and Toll-Like Receptor 4 Act Sequentially in Uptake and Intracellular Killing of Unopsonized Salmonella enterica Serovar Typhimurium by Human Neutrophils , 2007, Infection and Immunity.

[31]  A. Chakrabarti,et al.  Candida colonization and candidemia in a pediatric intensive care unit , 2008, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[32]  J. Laurini,et al.  Neonatal Candida parapsilosis meningitis and empyema related to epidural migration of a central venous catheter , 2008, Clinical Neurology and Neurosurgery.

[33]  M. Maiden,et al.  Candida orthopsilosis and Candida metapsilosis spp. nov. To Replace Candida parapsilosis Groups II and III , 2005, Journal of Clinical Microbiology.

[34]  S. Fridkin,et al.  Determining Risk Factors for Candidemia Among Newborn Infants From Population-Based Surveillance: Baltimore, Maryland, 1998–2000 , 2005, The Pediatric infectious disease journal.

[35]  M. Netea,et al.  Innate immune mechanisms for recognition and uptake of Candida species. , 2010, Trends in immunology.

[36]  W. Göpel,et al.  Galectin‐3 in cord blood of term and preterm infants , 2012, Clinical and experimental immunology.

[37]  A. Gácser,et al.  Targeted gene deletion in Candida parapsilosis demonstrates the role of secreted lipase in virulence. , 2007, The Journal of clinical investigation.

[38]  M. Ghannoum,et al.  Comparison of Biofilms Formed by Candidaalbicans and Candidaparapsilosis on Bioprosthetic Surfaces , 2002, Infection and Immunity.

[39]  S. Akira,et al.  Dectin-2 recognition of alpha-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans. , 2010, Immunity.

[40]  S. Filler,et al.  Host Cell Invasion and Virulence Mediated by Candida albicans Ssa1 , 2010, PLoS pathogens.

[41]  David W Williams,et al.  Characterization of Candida parapsilosis infection of an in vitro reconstituted human oral epithelium. , 2009, European journal of oral sciences.

[42]  J. Vazquez,et al.  Multiechinocandin- and Multiazole-Resistant Candida parapsilosis Isolates Serially Obtained during Therapy for Prosthetic Valve Endocarditis , 2005, Antimicrobial Agents and Chemotherapy.

[43]  U. Dilmen,et al.  Randomised controlled trial of prophylactic fluconazole versus nystatin for the prevention of fungal colonisation and invasive fungal infection in very low birth weight infants , 2010, Archives of Disease in Childhood: Fetal and Neonatal Edition.

[44]  D. Soll,et al.  Emergence of Fluconazole Resistance in a Candida parapsilosis Strain That Caused Infections in a Neonatal Intensive Care Unit , 2005, Journal of Clinical Microbiology.

[45]  B. Yoder,et al.  RESISTANT CANDIDA PARAPSILOSIS ASSOCIATED WITH LONG TERM FLUCONAZOLE PROPHYLAXIS IN AN ANIMAL MODEL , 2004, The Pediatric infectious disease journal.

[46]  Joseph M. Campos,et al.  Antifungal susceptibility of Candida spp. isolated from pediatric patients: a survey of 4 children's hospitals. , 2005, Diagnostic microbiology and infectious disease.

[47]  G. De Domenico,et al.  Ambroxol influences voriconazole resistance of Candida parapsilosis biofilm. , 2012, FEMS yeast research.

[48]  Y. Chou,et al.  Association of fungal colonization and invasive disease in very low birth weight infants. , 1998, The Pediatric infectious disease journal.

[49]  Alistair J. P. Brown,et al.  Immune Recognition of Candida albicans β-glucan by Dectin-1 , 2007 .

[50]  M. Pfaller,et al.  In Vitro Susceptibility of Invasive Isolates of Candida spp. to Anidulafungin, Caspofungin, and Micafungin: Six Years of Global Surveillance , 2007, Journal of Clinical Microbiology.

[51]  T. Walsh,et al.  Empirical therapy for neonatal candidemia in very low birth weight infants. , 2003, Pediatrics.

[52]  W. McGuire,et al.  Candida parapsilosis infection in very low birthweight infants , 2007, Archives of Disease in Childhood - Fetal and Neonatal Edition.

[53]  V. Anttila,et al.  Secular trend in candidemia and the use of fluconazole in Finland, 2004-2007 , 2010, BMC infectious diseases.

[54]  Y. Chou,et al.  Candidaemia in special care nurseries: comparison of albicans and parapsilosis infection. , 2000, The Journal of infection.

[55]  M. Maccani,et al.  High efficiency opsonin-independent phagocytosis of Candida parapsilosis by human neutrophils. , 2010, Medical mycology.

[56]  M. Cuenca‐Estrella,et al.  Prevalence and Susceptibility Profile of Candida metapsilosis and Candida orthopsilosis: Results from Population-Based Surveillance of Candidemia in Spain , 2008, Antimicrobial Agents and Chemotherapy.

[57]  T. Metsvaht,et al.  Risk factors associated with gut and nasopharyngeal colonization by common Gram-negative species and yeasts in neonatal intensive care units patients. , 2011, Early human development.

[58]  T. Kuijpers,et al.  Complement receptor 3, not Dectin-1, is the major receptor on human neutrophils for beta-glucan-bearing particles. , 2009, Molecular immunology.

[59]  A. Cassone,et al.  Vaginopathic and proteolytic Candida species in outpatients attending a gynaecology clinic. , 1991, Journal of clinical pathology.

[60]  M. Yamazaki,et al.  Comparison of proteinase, lipase and alpha-glucosidase activities from the clinical isolates of Candida species. , 2006, Japanese journal of infectious diseases.

[61]  D. Palazzi,et al.  Candida Non-albicans Versus Candida Albicans Fungemia in the Non-neonatal Pediatric Population , 2011, The Pediatric infectious disease journal.

[62]  M. Netea,et al.  Differential IL-17 Production and Mannan Recognition Contribute to Fungal Pathogenicity and Commensalism , 2010, The Journal of Immunology.

[63]  A. Gácser,et al.  A Rat Model of Neonatal Candidiasis Demonstrates the Importance of Lipases as Virulence Factors for Candida albicans and Candida parapsilosis , 2011, Mycopathologia.

[64]  M. Falagas,et al.  Relative frequency of albicans and the various non-albicans Candida spp among candidemia isolates from inpatients in various parts of the world: a systematic review. , 2010, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[65]  Choukri Ben Mamoun,et al.  Amino acids mediate colony and cell differentiation in the fungal pathogen Candida parapsilosis. , 2006, Microbiology.

[66]  Y. Carmeli,et al.  Factors associated with candidemia caused by non-albicans Candida species versus Candida albicans in the intensive care unit. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[67]  M. Maule,et al.  Routine Use of Fluconazole Prophylaxis in a Neonatal Intensive Care Unit Does Not Select Natively Fluconazole-Resistant Candida Subspecies , 2008, The Pediatric infectious disease journal.

[68]  S. Lockhart,et al.  Geographic Distribution and Antifungal Susceptibility of the Newly Described Species Candida orthopsilosis and Candida metapsilosis in Comparison to the Closely Related Species Candida parapsilosis , 2008, Journal of Clinical Microbiology.

[69]  Trees Jansen,et al.  Immune recognition of Candida albicans beta-glucan by dectin-1. , 2007, The Journal of infectious diseases.

[70]  M. Pires,et al.  Yeasts isolated from blood and catheter in children from a Public Hospital of São Paulo, Brazil , 2004, Mycopathologia.

[71]  A. Mitchell,et al.  How to build a biofilm: a fungal perspective. , 2006, Current opinion in microbiology.

[72]  N. Prasadarao,et al.  N-cadherin Mediates Endocytosis of Candida albicans by Endothelial Cells* , 2005, Journal of Biological Chemistry.

[73]  M. Simitsopoulou,et al.  Additive antifungal activity of anidulafungin and human neutrophils against Candida parapsilosis biofilms. , 2011, The Journal of antimicrobial chemotherapy.

[74]  L. Tomáška,et al.  Biology and genetics of the pathogenic yeast Candida parapsilosis , 2009, Current Genetics.

[75]  R. Auten,et al.  When to Suspect Fungal Infection in Neonates: A Clinical Comparison of Candida albicans and Candida parapsilosis Fungemia With Coagulase-Negative Staphylococcal Bacteremia , 2000, Pediatrics.

[76]  R. Hernández-Castro,et al.  Outbreak of Candida parapsilosis in a neonatal intensive care unit: a health care workers source , 2010, European Journal of Pediatrics.

[77]  N. Cerikcioglu,et al.  Acid proteinase, phospholipase and adherence properties of Candida parapsilosis strains isolated from clinical specimens of hospitalised patients , 2005, Mycoses.

[78]  A. Gácser,et al.  Candida parapsilosis, an Emerging Fungal Pathogen , 2008, Clinical Microbiology Reviews.

[79]  T. Walsh,et al.  Caspofungin Therapy of Neonates With Invasive Candidiasis , 2004, The Pediatric infectious disease journal.

[80]  T. Mayadas,et al.  The β-glucan receptor Dectin-1 activates the integrin Mac-1 in neutrophils via Vav protein signaling to promote Candida albicans clearance. , 2011, Cell host & microbe.

[81]  N. Jain,et al.  Epidemiology of Candidemia in a Tertiary Care Centre of North India: 5-Year Study , 2007, Infection.

[82]  M. Ghannoum,et al.  Differential in vitro activity of anidulafungin, caspofungin and micafungin against Candida parapsilosis isolates recovered from a burn unit. , 2009, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[83]  C. Vágvölgyi,et al.  In vitro interactions of Candida parapsilosis wild type and lipase deficient mutants with human monocyte derived dendritic cells , 2011, BMC Microbiology.

[84]  S. G. Monteiro,et al.  In vitro differential activity of phospholipases and acid proteinases of clinical isolates of Candida. , 2011, Revista da Sociedade Brasileira de Medicina Tropical.

[85]  L. Su,et al.  Genotyping analysis of colonizing candidal isolates from very-low-birthweight infants in a neonatal intensive care unit. , 2004, The Journal of hospital infection.

[86]  J. Sizun,et al.  Low rate of Candida parapsilosis-related colonization and infection in hospitalized preterm infants: a one-year prospective study. , 2001, The Journal of hospital infection.

[87]  William Oh,et al.  Neonatal Candidiasis Among Extremely Low Birth Weight Infants: Risk Factors, Mortality Rates, and Neurodevelopmental Outcomes at 18 to 22 Months , 2006, Pediatrics.

[88]  W. McGuire,et al.  Invasive fungal infection in very low birthweight infants: national prospective surveillance study , 2005, Archives of Disease in Childhood - Fetal and Neonatal Edition.

[89]  A. Cassone,et al.  Biotyping and Virulence Properties of Skin Isolates ofCandida parapsilosis , 1999, Journal of Clinical Microbiology.

[90]  J. Nosanchuk,et al.  Virulence of Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis in reconstituted human tissue models. , 2007, Fungal genetics and biology : FG & B.

[91]  A. Gácser,et al.  Candida parapsilosis fat storage-inducing transmembrane (FIT) protein 2 regulates lipid droplet formation and impacts virulence. , 2011, Microbes and infection.

[92]  J. Nosanchuk,et al.  Fatty Acid Synthase Impacts the Pathobiology of Candida parapsilosis In Vitro and during Mammalian Infection , 2009, PloS one.

[93]  G. Fadda,et al.  Biofilm Production by Candida Species and Inadequate Antifungal Therapy as Predictors of Mortality for Patients with Candidemia , 2007, Journal of Clinical Microbiology.

[94]  P. Horváth,et al.  The identification of gene duplication and the role of secreted aspartyl proteinase 1 in Candida parapsilosis virulence. , 2012, The Journal of infectious diseases.

[95]  D. Stevens,et al.  Candida parapsilosis: a review of its epidemiology, pathogenesis, clinical aspects, typing and antimicrobial susceptibility , 2009, Critical reviews in microbiology.

[96]  David L. Williams,et al.  Dectin‐1 promotes fungicidal activity of human neutrophils , 2007, European journal of immunology.

[97]  Ken Jacobson,et al.  A Novel Pseudopodial Component of the Dendritic Cell Anti-Fungal Response: The Fungipod , 2010, PLoS pathogens.

[98]  W. McGuire,et al.  Prophylactic systemic antifungal agents to prevent mortality and morbidity in very low birth weight infants. , 2007, The Cochrane database of systematic reviews.

[99]  Ronald N. Jones,et al.  Variation in Candida spp. distribution and antifungal resistance rates among bloodstream infection isolates by patient age: report from the SENTRY Antimicrobial Surveillance Program (2008-2009). , 2010, Diagnostic microbiology and infectious disease.

[100]  P. Ricciardi-Castagnoli,et al.  Dendritic Cells Discriminate between Yeasts and Hyphae of the Fungus Candida albicans , 2000, The Journal of experimental medicine.

[101]  E. Badran,et al.  Epidemiological characteristics of Candida species colonizing oral and rectal sites of Jordanian infants , 2011, BMC pediatrics.

[102]  D. Moyes,et al.  Activation of MAPK/c-Fos induced responses in oral epithelial cells is specific to Candida albicans and Candida dubliniensis hyphae , 2011, Medical Microbiology and Immunology.

[103]  I. Pichová,et al.  Two aspartic proteinases secreted by the pathogenic yeast Candida parapsilosis differ in expression pattern and catalytic properties , 2009, Biological chemistry.

[104]  M. C. Furlaneto,et al.  Haemolytic and proteinase activities in clinical isolates of Candida parapsilosis and Candida tropicalis with reference to the isolation anatomic site , 2011, Mycoses.

[105]  J. Nosanchuk,et al.  Lipid droplet formation protects against gluco/lipotoxicity in Candida parapsilosis: An essential role of fatty acid desaturase Ole1 , 2011, Cell cycle.

[106]  J. Bliss,et al.  Oxidative burst and phagocytosis of neonatal neutrophils confronting Candida albicans and Candida parapsilosis. , 2009, Early human development.

[107]  L. Rubin,et al.  Emergence of Candida parapsilosis as the predominant species causing candidemia in children. , 1998, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[108]  Benjamin J Park,et al.  Candidemia in Neonatal Intensive Care Units: Barcelona, Spain , 2006, The Pediatric infectious disease journal.